There are many devices for administering powdered medicaments to the lungs, which employ propellants, such as compressed gases, e.g. air, or liquefied gas propellants, to dispense and disperse the medicament.
There are also a number of known breath actuated inhalation devices for administering powdered medicaments to the lungs, which have mouthpieces through which the medicament is inhaled. British Patent Specification Nos. 1 521 000, 1 520 062, 1 472 650 and 1 502 150 disclose more complex devices in which a complete capsule is inserted into the device thus ensuring no spillage of medicament prior to inhalation, and access to the medicament is gained by piercing the capsule or cutting it in half, inside the dispensing device. On inhalation the air flows into or through the capsule and the powder within is released into the air stream and flows towards the mouth.
U.S. Pat. No. 4,210,140 discloses a device in which access to the powdered medicament is gained by pulling the halves of the capsule apart so that the medicament is emptied to a suitable position for entrainment in the airflow caused by inhalation.
U.S. Pat. No. 6,655,381B2 relates to a pre-metered dose assembly for consistently supplying precise doses of medicament for a breath-actuated dry powder inhaler. The assembly includes a cap defining a dry powder delivery passageway for providing air to a dry powder supply port of a swirl chamber of a breath-actuated dry powder inhaler, and a magazine including a plurality of reservoirs for holding pre-metered doses of dry powder. One of the magazine and the cap is movable with respect to the other of the magazine and the cap for sequentially positioning the reservoirs within the delivery passageway of the cap. A breath-induced low pressure at an outlet port of the inhaler causes an airflow through the dry powder delivery passageway of the assembly and into the dry powder supply port that entrains dry powder from the reservoir positioned in the passageway for inhalation by a patient using the inhaler. The passageway is provided with a venturi in the passageway by the reservoir to create a flow through the reservoir and bring the powder there from.
U.S. Pat. No. 4,446,862 (Baum et al.) describes an inhaler device in which access to the powdered medicament is gained by pulling the halves of a capsule apart, leaving the lower half of the capsule retained in an upright position in the device, with its open end flush with the lower surface of a disc shaped inhalation chamber. Spaced around half the circumference of the chamber are a number of air inlets and, opposite these, a larger air outlet leading to a mouthpiece. On inhalation, air is drawn through the chamber and across the open mouth of the capsule. It is stated that this may create a resonance effect in the capsule, similar to the effect which causes a sound to be produced by blowing across the opening of a bottle.
US published patent application number 2009114220 (Boehringer) discloses a powder inhaler device in which a powder cavity is provided with an air outlet opening into the lower surface of an air flow path which narrows in the region of the outlet opening. The cavity also has an air inlet which does not open into the flow path. A venturi is created by the narrowing flow path adjacent the outlet, giving rise to low pressure in this area when flow is generated by a user inhaling. Air is thereby drawn through the cavity from the inlet to the outlet and then into the flow path.
US2009/0084379 (Baxter) describes a single dose inhaler suitable for insulin. The medicament is stored in a cavity with a round or oval shaped opening. The cavity has a depth greater than its length in the flow direction. A flow passage from an inlet to a mouthpiece passes across the top of the cavity; the floor and ceiling of the passage are smoothly curved and diverge on the upstream and downstream sides of the cavity, with the narrowest part of the passage adjacent the cavity. A “driven cavity flow” is said to be created in the cavity so that powder is drawn out of the cavity and into the air flow.
WO2009/152477 (Mannkind) discloses a single dose inhaler suitable for insulin, with a medicament storage cavity which is deeper than it is long in the flow direction. The cavity has a lid in which one or more outlet holes are formed, whilst an inlet is formed in the upper downstream wall of the cavity. In use, air is drawn into the inlet and a circulating air flow is created which exits upwardly out of the outlet hole(s) in the lid.
In spite of the numerous prior art devices there is a need for a device, particularly a multi-cavity inhaler device, which is simple in design and therefore inexpensive, compact in size and also simple to operate, but which also allows for efficient emptying of a cavity of powder. Consistent and efficient emptying is important partly to avoid wastage of expensive medicament by leaving it in the device, but more importantly to avoid residual powder contaminating the device and being inadvertently inhaled on subsequent uses of the device.
There is also a need for a device which efficiently deaggregates powder before being administered. It is desirable for the deaggregation process to result in a significant proportion of the powder particles being in a certain aerodynamic size range. This is often referred to as classifying the powder particles. Various ways of enabling deaggregation are described in the prior art. For example, tortuous flow paths can cause deaggregation as particles impact the walls of the flow path. Alternatively, obstructions can be placed in the flow path downstream of the powder cavity or reservoir. Vibrating or shaking is another possibility. U.S. Pat. No. 4,446,862, discussed above, provides for the capsule to be moved rapidly on inhalation to loosen the powder contents and thereby aid deaggregation of highly cohesive or compacted powders.
Devices employing deaggregation features in the downstream flow passage may become clogged or contaminated in use, since medicament powder may accumulate on these downstream features. It is of course desirable to reduce or avoid the risk of administering an inaccurate amount of medicament powder. Where powder accumulates on downstream deaggregation features, a risk is that accumulated powder from several doses may dislodge suddenly from these downstream features (e.g. if the device is dropped) resulting in the patient receiving a significant over-dose.
It is an object of the invention at least to mitigate some or all of the above problems.
The trend in dry powder inhaler devices is to have shallow cavities into which flow is directed in order to entrain particles and empty the cavity efficiently. Especially for larger doses of powder, the use of shallow cavities can result in devices which are relatively large, since such a cavity may occupy a relatively large area.
The inventors have found, surprisingly, that a relatively deep cavity may be emptied very efficiently by optimizing the design parameters of the device to maximize the phenomenon of shear driven cavity flow in the powder cavity. The inventors have investigated a number of different cavity shapes and geometric parameters for a cavity and the flow path over the cavity, and compared emptying and deaggregating efficiency for these using both computational fluid dynamics techniques and physical prototypes.
The concept of shear driven cavity flow is, generally speaking, that a rotating flow in a cavity may result from passing a fluid stream across the opening of the cavity (distinct from directing flow into the cavity or using an airflow to create low pressure by the venturi effect above an opening of the cavity to draw a fluid stream through it). The flow tends to rotate in a cylindrical pattern.
U.S. Pat. No. 4,446,862, referred to above, describes a device in which a stream of air is passed across the opening of the separated lower half of a standard pharmaceutical capsule, thereby entraining powder. The inventors of the present invention believe that some shear driven cavity flow may occur in this prior device and that this phenomenon may partially explain the reported results. However, the inventors believe shape of the cavity may not allow the cylindrically rotating flow pattern characteristic of shear driven cavity flow to develop.
US2009/0084379 (Baxter) referred to above appears to use the shear driven flow phenomenon, but again the inventors believe the shape of the cavity and/or flow path may not be optimal.
It is somewhat counter-intuitive that generating a cylindrical rotating flow in a powder-containing cavity may result in fast and effective emptying of the cavity, rather than simply causing powder to be entrained in the rotating flow. However, the inventors of the present invention have found that powder may be quickly transferred from the rotating flow to the linear flow over the cavity, rather than remaining for a long period entrained in the rotating flow.
The inventors have found that the shear driven cavity flow effect, preferably in a relatively deep cavity, may be optimized by manipulating one or more parameters such as flow path design, cavity shape, pressure drop, flow velocity or volume flow rate. The inventors have found, surprisingly, that not only fast cavity emptying but also deaggregation or classifying of powder in the cavity can be achieved very effectively in a deep cavity by employing the shear driven cavity flow phenomenon.